Beyond insulin resistance

Insulin resistance has long been linked to laminitis, a potentially devastating inflammatory condition of the hoof. Insulin, a hormone produced by the pancreas, enables the body’s cells to utilize sugar (glucose), their primary source of fuel. When resistance develops, however, cells stop responding to insulin and the resulting rise in the hormone’s levels in the blood can lead to laminitis.

Now, research shows that even when the horse’s body reacts normally to insulin, the hormone can nonetheless become part of a cascade of events that leads to laminitis. These findings may not only prompt a change in the terms used to discuss the relationship between insulin and laminitis but will also have implications for the diagnosis and management of at-risk horses.

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MEALS AND METABOLISM

Nearly everything your horse eats contains starches and sugars that are converted to glucose during digestion, which in turn is used as energy for cells throughout the body. Grains have more, hay generally has less, but every time your horse eats, he’s taking in glucose precursors. As meals are digested, the stomach and small intestine absorb glucose and then release it into the bloodstream. From there, it’s used immediately by cells or stored for later use. Insulin is critical to both of those processes.

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Beta cells in the pancreas monitor the level of glucose in the blood, and when they detect an increase, they produce insulin, which travels to cells all over the body. The more glucose there is in the blood, the more insulin is produced for utilization.

“Insulin binds to receptors on cells to ‘open the door,’ as it were, and allow glucose to leave the bloodstream and go into those tissues,” explains Shannon Pratt-Phillips, PhD, of North Carolina State University. Insulin also helps transform excess glucose into larger molecules called glycogen, which are then stored in the liver or muscle.

A major function of insulin is to “regulate” blood glucose concentration ---to keep glucose levels from remaining elevated---so when the hormone is working efficiently, blood glucose is described as “regulated.” After a horse eats a meal, insulin is released in response to the glucose produced during digestion, blood glucose concentration drops steadily and insulin production decreases accordingly.

Sometimes, however, this process goes awry. Probably the most common problem is a condition called insulin resistance, which occurs when the hormone is unable to “unlock” the door to cells. “Somewhere along that route, insulin is not functioning properly,” explains Pratt-Phillips, “and glucose, unable to enter cells, remains in the blood. If the blood glucose concentrations stay high, more insulin will be released from the pancreas to try to deal with that glucose. This cycle continues and results in more and more insulin being released.”

In people, insulin resistance can progress to type 2 diabetes. Horses with insulin resistance tend to develop a range of problems, collectively referred to as equine metabolic syndrome (EMS). The most devastating aspect of EMS is a susceptibility to laminitis (see “The Facts on EMS,” page 47).

MORE THAN RESISTANCE

Horses with EMS are at higher risk of laminitis and they often are found to be insulin resistant. So you might assume those conditions are dependent on each other. But it’s not that straightforward.

“When we first described EMS, about 15 years ago, the emphasis was on insulin resistance,” says Philip Johnson, BVSc, MRCVS, of the University of Missouri. “It has now shifted. Work done in Australia in 2007 showed that high blood insulin levels represent, in and of themselves, a risk factor for laminitis. Anytime a horse or pony has a higher-than-normal blood insulin there is a risk for developing laminitis. This is like an insulin toxicity.”

The problem may start earlier in the digestive process, he explains. “The new way of looking at EMS is that the horses and ponies with it have an intestinal system that absorbs a lot of glucose compared to other horses,” says Johnson. “Along with that comes an increased pancreatic insulin secretion response.” In other words, the horse’s body is so efficient in absorbing glucose from meals that the pancreas simply produces too much insulin in response.

Based on this information, many researchers are adopting a new vocabulary for discussing insulin. “Today the term ‘insulin dysregulation’ is more appropriate for this problem in horses than just calling it insulin resistance,” says Nicholas Frank, DVM, PhD, of Tufts University. The technical term would be postprandial hyperinsulinaemia, which refers to an excessively high level of insulin in the blood after eating. Certain types of horses, particularly ponies, have a genetic predisposition to postprandial hyperinsulinaemia, which may be linked to other hormonal imbalances or the malfunction of enzymes within the pancreas or small intestine.

Frank says that postprandial hyperinsulinaemia may be the earliest stage of insulin resistance in these genetically predisposed horses. It may even induce resistance directly by desensitizing the receptors on cells or encouraging the development of fat accumulations, which then may further impede insulin function. “There are some studies looking at the biological activity (and inflammatory mediator production) within these regions of adiposity, and I think they make insulin dysregulation worse as they appear and enlarge,” he says.

The working theory now is that certain horses are born with a genetic predisposition to hyperinsulinaemia, which---if not diagnosed and managed ---can lead to insulin resistance and the clinical signs of EMS, including laminitis. “If we think about a time course with this syndrome, we realize that the animal is born with these genetics, and that’s the hand it is dealt. As it grows older, how that horse is managed in its feed, environment and exercise will determine whether those genetics actually lead to a medical problem,” says Frank.

TESTING, TESTING

The growing understanding of hyperinsulinaemia and insulin resistance has resulted in an altered approach to testing for EMS, with an increasing emphasis on identifying horses in the earliest stages, before the condition can progress.

Insulin resistance alone can be identified through a simple blood test performed after at least six hours of fasting. “If the insulin concentration is above 20 micro-units per milliliter [after fasting] the horse is said to be insulin resistant,” says Pratt-Phillips. “I would consider the horse mildly insulin resistant in that lower end, while others may have very high levels. I’ve seen some horses with a resting insulin level as high as 90 to 100 every single day,” she says. The trouble with this test is the wide variations among individual horses. Pratt-Phillips often recommends a second test a few days later to double-check borderline cases.

An even more informative test for insulin resistance involves administering glucose intravenously to the horse, followed by soluble insulin, and then periodically taking blood samples to track the rise and then fall of both in the bloodstream. These tests tend to be more expensive, but they provide more information about a horse’s specific and dynamic response to glucose levels in the blood.

In light of research into postprandial hyperinsulinaemia, Frank also recommends an oral sugar test to identify horses in the earlier stages of insulin dysfunction. “When we just do an IV test, we will certainly find the horses with insulin resistance, but only those that are moderately to severely affected,” he says. “What we really want to do, with a diagnostic test, is discover the mildly affected horse early on, so we have a chance to change the management of that horse---and prevent laminitis and all the downstream effects of this syndrome.”

Testing for EMS, then, will ideally become a two-step process. “We still recommend testing the animal’s insulin resistance using a blood test after fasting, but we add to that the oral sugar test so we have to look at two sides of this---the oral response to food with the standardized sugar test, and a test for insulin sensitivity,” Johnson says.

Frank advocates looking for insulin issues even as part of routine physical examinations. “The more we can find these problems during annual or biannual wellness evaluations, and head them off, the less laminitis we will be treating. No veterinarian wants to have to treat laminitis because it is a disastrous disease once it occurs. If we can all focus on prevention rather than treatment of laminitis, this would be a major advance in veterinary care.”

TAKING CONTROL

Sorting out the complexities of insulin dysregulation could take researchers years, but that doesn’t mean it’s too soon to take management steps to protect your horse. In fact, preventive measures are pretty much the same whether a horse has insulin resistance or postprandial hyperinsulinaemia. They include:

• Reduce sugars in the horse’s diet. “If we have horses who have a higher insulin concentration, we know that keeping them on a low-sugar diet does not stimulate insulin release as much,” says Frank. Remember that carbohydrates are converted to sugars in the body, so you’ll want to remove not just molasses-based feeds from an at-risk horse’s ration but probably all grain.

“Most of the horses that are insulin resistant don’t need any grain. They may just need some vitamins/minerals or a protein supplement,” says Johnson. “Unless they are doing a lot of work or producing milk, horses don’t need extra calories. So if you have a horse who is insulin resistant, consider providing a balancer supplement to meet his nutritional needs and eliminating grain entirely.”

If a horse does need additional calories in the form of grain, be sure to select an appropriate mixture. “Horse owners can look for grains that have a low glycemic index, so that when the horse eats, his blood glucose doesn’t go up very high,” says Brian Nielsen, PhD, of Michigan State University. “For the insulin-resistant horse, this makes sense.” There are a number of low glycemic commercial feeds on the market today specifically developed to fill this need.

Hay can also be high in sugar, but the only way to know is to have a sample tested. Your local agriculture extension agent, based at a land-grant university, can help you arrange for testing. “If hay has a lot of sugar, you can soak it in water to remove much of the sugar,” says Johnson. Depending on the type of hay, he adds, several hours of soaking may be required to satisfactorily reduce the sugar content.

• Feed frequent small meals. When feeding horses, the closer you can get to mimicking natural grazing behavior, the better. Horses who eat all day long do not have the dramatic and damaging spikes in blood glucose and insulin that occur when fewer, larger meals are served. Arranging to have grain doled out more than twice a day can be difficult, but it’s fairly easy to provide continuous access to hay using a slow feeder or hay net with smaller holes.

Pratt-Phillips conducted a series of studies examining the effect of meal duration on blood-glucose spikes. To extend the length of grain meals, for example, she added balls to the feed tub. “Some people use large, smooth rocks,” she says. “The horse has to work around those while trying to eat grain, which slows the intake.” Pratt-Phillips found that when it took horses longer to eat, blood glucose spikes were minimized. “Anything that stretches out/prolongs the feeding, along with providing smaller meals throughout the day, can be helpful to blunt those glucose concentrations,” she says.

• Restrict grazing. Lush, fast- growing grass is high in soluble carbohydrates, which can raise blood glucose and insulin levels. “You often hear of horses developing laminitis when turned out on fresh pasture in the spring. These are usually not the horses that are athletic and lean, but the easy keeper or pony that tends to be insulin-resistant,” says Johnson.

Spring pasture is not the only risk. Pastures undergoing growth spurts in the fall and grasses rebounding from drought can also be high in sugars. The safest bet for a horse with EMS is no pasture at all, but if that’s not possible, restricting grazing with a well-fitting muzzle is crucial to protecting his health.

Pratt-Phillips also recommends keeping an eye on the clock. “Sugars rise during the day (with sunlight) so those concentrations tend to be highest in the late afternoon,” she says. “If horses are insulin resistant, you’d let them out on pasture first thing in the morning when those levels are lowest, and just for a couple of hours, using a grazing muzzle.”

• Don’t let the horse become fat. Obesity is likely a cause as well as an effect of EMS, so it’s doubly important to keep horses at a healthy weight--- typically considered a body condition score (BCS) of 6 or below. But don’t get hung up on the number: A horse with a lower BCS score can still have a cresty neck, an indication of insulin troubles. Researchers are even working on developing a “cresty neck score” that correlates to laminitis risk, but in the meantime you’ll likely know one when you see one.

Dietary changes will help take weight off a horse, but they will be even more effective when paired with increased exercise. If your fat, insulin-troubled horse isn’t lame or sore from laminitis, start him on an exercise program that includes active turnout as well as regular riding. In addition to burning excess calories, exercise helps increase a horse’s sensitivity to insulin, which can counter the underlying problem. It may take weeks of daily, long rides to reduce the weight on a horse genetically predisposed to holding onto it, but the effort is well worth it.

This article was originally published the April 2016 issue, Volume #475 of EQUUS magazine